Fernandez Hubert H, Standaert David G, Hauser Robert A, Lang Anthony E, Fung Victor S C, Klostermann Fabian, Lew Mark F, Odin Per, Steiger Malcolm, Yakupov Eduard Z, Chouinard Sylvain, Suchowersky Oksana, Dubow Jordan, Hall Coleen M, Chatamra Krai, Robieson Weining Z, Benesh Janet A, Espay Alberto J
Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA.
Mov Disord. 2015 Apr;30(4):500-9. doi: 10.1002/mds.26123. Epub 2014 Dec 24.
Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. L-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces L-dopa-plasma-level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day "off" time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, "on" time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks.
帕金森病（PD）的运动并发症与长期口服左旋多巴治疗相关，且与脉冲式多巴胺能刺激有关。左旋多巴-卡比多巴肠凝胶（LCIG）通过经皮内镜下胃空肠造瘘管（PEG-J）持续给药，这可减少左旋多巴血浆水平波动，并可能转化为运动并发症的减少。我们展示了最大规模的国际前瞻性54周开放标签LCIG研究的最终结果。尽管接受了优化治疗，但仍有严重运动波动（每天“关”期>3小时）的PD患者接受了LCIG单药治疗。在开始使用LCIG后>28天允许使用其他PD药物。安全性是通过不良事件（AE）、器械并发症和完成治疗的患者数量来衡量的主要终点。次要终点包括日记评估的“关”期时间、有/无麻烦异动症的“开”期时间、统一帕金森病评定量表（UPDRS）以及健康相关生活质量（HRQoL）结果。在354名入组患者中，324名（91.5%）接受了PEG-J，272名（76.8%）完成了研究。大多数AE为轻度/中度且短暂；器械插入并发症（34.9%）是最常见的。27名（7.6%）患者因AE退出。严重AE发生在1
